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SARS-CoV-2 spike protein (SARS-2-S) induced cell-cell fusion in uninfected cells may occur in long COVID-19 syndrome, as circulating SARS-2-S or extracellular vesicles containing SARS-2-S (S-EVs) were found to be prevalent in post-acute sequelae of COVID-19 (PASC) for up to 12 months after diagnosis. Although isolated recombinant SARS-2-S protein has been shown to increase the SASP in senescent ACE2-expressing cells, the direct linkage of SARS-2-S syncytia with senescence in the absence of virus infection and the degree to which SARS-2-S syncytia affect pathology in the setting of cardiac dysfunction are unknown. Here, we found that the senescent outcome of SARS-2-S induced syncytia exacerbated heart failure progression. We first demonstrated that syncytium formation in cells expressing SARS-2-S delivered by DNA plasmid or LNP-mRNA exhibits a senescence-like phenotype. Extracellular vesicles containing SARS-2-S (S-EVs) also confer a potent ability to form senescent syncytia without de novo synthesis of SARS-2-S. However, it is important to note that currently approved COVID-19 mRNA vaccines do not induce syncytium formation or cellular senescence. Mechanistically, SARS-2-S syncytia provoke the formation of functional MAVS aggregates, which regulate the senescence fate of SARS-2-S syncytia by TNFα. We further demonstrate that senescent SARS-2-S syncytia exhibit shrinked morphology, leading to the activation of WNK1 and impaired cardiac metabolism. In pre-existing heart failure mice, the WNK1 inhibitor WNK463, anti-syncytial drug niclosamide, and senolytic dasatinib protect the heart from exacerbated heart failure triggered by SARS-2-S. Our findings thus suggest a potential mechanism for COVID-19-mediated cardiac pathology and recommend the application of WNK1 inhibitor for therapy especially in individuals with post-acute sequelae of COVID-19.
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COVID-19 , Senescência Celular , Células Gigantes , Insuficiência Cardíaca , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/virologia , Animais , Células Gigantes/virologia , Células Gigantes/metabolismo , Células Gigantes/patologia , COVID-19/metabolismo , COVID-19/complicações , COVID-19/virologia , COVID-19/patologia , Humanos , Glicoproteína da Espícula de Coronavírus/metabolismo , Camundongos , Vesículas Extracelulares/metabolismoRESUMO
Dry eye disease (DED) is a common ocular condition affecting a significant portion of the global population, yet effective treatment options remain elusive. This study investigates the therapeutic potential of M2 macrophage-derived extracellular vesicles (M2-EVs) in a mouse model of DED. The DED model was established using 0.2% benzalkonium chloride (BAC) eye drops, applied twice daily for a week. Post induction, the mice were categorized into 5 groups: PBS, Sodium Hyaluronate (HA, 0.1%), Fluoromethalone (FM, 0.1%), M0-EVs, and M2-EVs. The efficacy of M2-EVs was assessed through tear production, corneal fluorescein staining and HE staining. RNA sequencing (RNA-seq) was employed to investigate the mechanisms underlying the therapeutic effects of M2-EVs in DED. Notably, the M2-EVs treated group exhibited the highest tear secretion, indicating improved tear film stability and reduced corneal surface damage. Histological analysis revealed better corneal structure organization in the M2-EVs group, suggesting enhanced ocular surface repair and corneal preservation. Furthermore, M2-EVs treatment significantly decreased pro-inflammatory cytokine levels and showed unique enrichment of genes related to retinal development. These findings suggest that M2-EVs could serve as a promising noninvasive therapeutic approach for human DED, targeting ocular surface inflammation.
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Ionic liquids (ILs) are an extremely exciting class of electrolytes for energy storage applications. Upon dissolving alkali metal salts, such as Li or Na based salts, with the same anion as the IL, an intrinsically asymmetric electrolyte can be created for use in batteries, known as a salt-in-ionic liquid (SiIL). These SiILs have been well studied in the bulk, where negative transference numbers of the alkali metal cation have been observed from the formation of small, negatively charged clusters. The properties of these SiILs at electrified interfaces, however, have received little to no attention. Here, we develop a theory for the electrical double layer (EDL) of SiILs where we consistently account for the thermoreversible association of ions into Cayley tree aggregates. The theory predicts that the IL cations first populate the EDL at negative voltages, as they are not strongly bound to the anions. However, at large negative voltages, which are strong enough to break the alkali metal cation-anion associations, these IL cations are exchanged for the alkali metal cation because of their higher charge density. At positive voltages, we find that the SiIL actually becomes more aggregated while screening the electrode charge from the formation of large, negatively charged aggregates. Therefore, in contrast to conventional intuition of associations in the EDL, SiILs appear to become more associated in certain electric fields. We present these theoretical predictions to be verified by molecular dynamics simulations and experimental measurements.
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OBJECTIVE: To investigate the practical value of the transrectal two-dimensional shear-wave elastography (SWE) in benign prostatic hyperplasia (BPH). METHODS: Consecutive male participants with and without BPH constituted the BPH and control group respectively were enrolled prospectively between March and December 2022. Transrectal conventional ultrasound and SWE examinations for the prostate were performed on these participants. Data of quantitative stiffness of the transitional zone (TZ) and peripheral zone (PZ) of prostate, volume of prostate (VP) and volume of TZ (VTZ) and prostate specific androgen (PSA), etc., were collected. Linear regression analyses were used to investigate the associations between quantitative stiffness data and other clinical parameters. RESULTS: There were 200 participants evaluated, including 100 healthy participants and 100 BPH patients. For every one-year increment in age, it was correlated with 0.50 kPa increasement of TZ stiffness. VP and VTZ were correlated with TZ stiffness. Higher TZ stiffness was associated with higher free prostate specific antigen (PSA) and total PSA. CONCLUSIONS: The prostate is stiffer and larger in BPH group compared to control group. Quantitative stiffness of the TZ was related with age, VP, VTZ and PSA.
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Técnicas de Imagem por Elasticidade , Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos de Casos e Controles , Próstata/diagnóstico por imagem , Antígeno Prostático Específico/sangueRESUMO
Nontoxic, highly sensitive InP quantum dot (QD) fluorescent immunoassay probes are promising biomedical detection modalities due to their unique properties. However, InP-based QDs are prone to surface oxidation, and the stability of InP QD-based probes in biocompatible environments remains a crucial challenge. Although the thick shell can provide some protection during the phase transfer process of hydrophobic QDs, the photoluminescence quantum yield (PLQY) is generally decreased because of the contradiction between lattice stress relaxation and thick shell growth. Herein, we developed thick-shell InP-based core/shell QDs by inserting a ZnSeS alloy layer. The ternary ZnSeS intermediate shell could effectively facilitate lattice stress relaxation and passivate the defect states. The synthesized InP/ZnSe/ZnSeS/ZnS core/alloy shell/shell QDs (CAS-InP QDs) with nanostructure tailoring revealed a larger size, high PLQY (90%), and high optical stability. After amphiphilic polymer encapsulation, the aqueous CAS-InP QDs presented almost constant fluorescence attenuation and stable PL intensity under different temperatures, UV radiation, and pH solutions. The CAS-InP QDs were excellent labels of the fluorescence-linked immunosorbent assay (FLISA) for detecting C-reactive protein (CRP). The biotin-streptavidin (Bio-SA) system was first introduced in the FLISA to further improve the sensitivity, and the CAS-InP QDs-based SA-Bio sandwich FLISA realized the detection of CRP with an impressive limit of detection (LOD) of 0.83 ng/mL. It is believed that the stable and sensitive InP QD fluorescent probes will drive the rapid development of future eco-friendly, cost-effective, and sensitive in vitro diagnostic kits.
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Nanoestruturas , Pontos Quânticos , Biotina , Estreptavidina , Corantes Fluorescentes , LigasRESUMO
BACKGROUND AND AIM: Identifying a more suitable marker among various measures of adiposity, demonstrating strong associations and predictive ability for clinical use, remains a topic of debate. Weight-adjusted waist index (WWI) has been proposed as a novel index of adiposity, yet its exploration is limited, especially in Chinese populations. This study seeks to examine the associations between body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHTR), weight-adjusted waist index (WWI), waist circumference divided by body mass to the power of 0.333 (WC/M0.333), visceral adiposity index (VAI), lipid accumulation product (LAP), and the incidence of diabetes, cardiovascular disease, and non-accidental mortality in Chinese populations. Furthermore, our goal is to compare the respective predictive values of these measures for these health outcomes. METHODS AND RESULTS: This prospective cohort study included 21,750 subjects with a 9-year follow-up period. Cox proportional hazard models were used to investigate the relationship between eight anthropometric indexes and the incidence of diabetes, cardiovascular disease, and non-accidental mortality. The predictive value of these eight indexes was compared using the area under the curve metric. Significant positive associations were found between WWI and the risk of diabetes. Using the first quartile (Q1) of WWI as the reference group, hazard ratios with 95% confidence intervals for the risk of diabetes were 1.58 (0.98-2.55) for Q2, 2.18 (1.34-3.35) for Q3, and 2.27 (1.41-3.67) for Q4. Significant associations were observed with the highest quartile of WWI for the risk of cardiovascular disease [Q2: HR 1.45 (95% CI 1.06-1.98); Q3: 1.33 (0.97-1.83); Q4: 1.55 (1.13-2.14)] and risk of non-accidental mortality [Q2: 0.94 (0.80-1.11); Q3: 1.24 (1.04-1.48); Q4: 1.44 (1.16-1.79)]. Receiver operating characteristic analysis revealed that WWI exhibited superior discrimination and accuracy in predicting cardiovascular disease and non-accidental mortality compared to other adiposity indexes (BMI, WC, WHR, WHTR, WC/M0.333, VAI, and LAP). CONCLUSION: WWI exhibited the most robust and consistent association with the incidence of cardiovascular disease and non-accidental mortality. Given its simplicity and widespread use, WWI emerges as a novel and practical predictor of diabetes, cardiovascular disease, and non-accidental mortality among the eight adiposity indexes investigated in this study.
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OBJECTIVES: To compare the clinical efficacy and safety of single-use and reusable digital flexible ureteroscopy for the treatment of lower pole stones. METHODS: We enrolled 135 patients underwent reusable flexible ureteroscopy (FURS) and 78 patients underwent single-use digital FURS. Demographic, clinical variables, anatomical parameters of the lower calyx and perioperative indicators were compared in the two groups. RESULTS: Thirty-six patients in the infundibuloureter angle (IPA) < 45° subgroup had a mini-percutaneous nephrolithotomy (mini-PCNL), including 25 patients in the reusable FURS group and 11 patients in the single-use FURS group. The demographic and clinical variables in the two FURS groups were comparable. There was no statistical difference in the success rate of stone searching (P > 0.05). In terms of the success rate of lithotripsy, there was also no statistical difference in the IPA ≥ 45° subgroup (P > 0.05), whereas single-use FURS was superior in the IPA < 45° subgroup (χ2 = 6.513, P = 0.011). The length of the working fiber in the reusable FURS and single-use FURS groups was 3.20 ± 0.68 mm and 1.75 ± 0.47 mm, respectively (t = 18.297, P < 0.05). The use of a stone basket in the reusable FURS (31/135, 23.0%) was significantly higher than that in the single-use FURS (8/78, 10.3%) (χ2 = 5.336, P = 0.021). Compared with the reusable FURS group, the single-use FURS group had shorter operation times (P < 0.05) and higher stone-free rate (SFR) (χ2 = 4.230, P = 0.040). There was no statistical difference in the intraoperative transfer of mini-PCNL and postoperative complications between the two groups (P > 0.05). CONCLUSIONS: Single-use and reusable FURS are alternative methods for removal of lower pole stones (i.e., 2 cm or less). Single-use FURS has a high success rate of lithotripsy, shorter operation time, and high stone-free rate.
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Reutilização de Equipamento , Cálculos Renais , Ureteroscópios , Ureteroscopia , Humanos , Ureteroscopia/métodos , Ureteroscopia/instrumentação , Masculino , Feminino , Estudos Retrospectivos , Cálculos Renais/cirurgia , Pessoa de Meia-Idade , Adulto , Estudos de Casos e Controles , Resultado do Tratamento , Desenho de Equipamento , Equipamentos Descartáveis , IdosoRESUMO
BACKGROUND: Studies on the association between estimated cardiorespiratory fitness (CRF) and changes in metabolic risk in the Chinese population are limited. This study aims to examine the associations between CRF and changes in metabolic risk. SUBJECTS AND METHODS: We included 4,862 and 2,700 participants recruited from 28 provinces in the China Health and Retirement Longitudinal Study (CHARLS) in the baseline (Wave 1) and follow-up (Wave 4) analyses, respectively. CRF was calculated using sex-specific longitudinal non-exercise equations. Metabolic indicators included systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and fasting plasma glucose (FPG) levels. The metabolic score was calculated as the number of changes in the above metabolic indicators above the 75th percentile of the distribution of changes (equal to or below the 25th percentile for HDL-C). RESULTS: In the baseline analysis, CRF was negatively associated with SBP, DBP, TG, and FPG, and positively correlated with HDL-C after adjusting for age, smoking status, and drinking status (all P < 0.0001) in both males and females. In the follow-up analysis, higher baseline CRF was significantly related to a decrease in SBP, DBP, TG, FPG, and metabolic score (all P < 0.0005), and increased HDL-C (P < 0.0001) after further adjustment for corresponding baseline metabolic indicators. The associations remained significant after stratification by sex, except for the changes in HDL-C levels in females. Furthermore, improved CRF was associated with favorable changes in DBP, TG, HDL-C, FPG, and metabolic scores in all populations and males. Significant associations between changes in CRF and DBP, TG, and FPG levels were found in females. CONCLUSION: Higher baseline CRF and improved CRF were associated with favorable changes in metabolic indicators.
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Aptidão Cardiorrespiratória , Masculino , Feminino , Humanos , Aptidão Cardiorrespiratória/fisiologia , Estudos Longitudinais , Estudos Prospectivos , Triglicerídeos , Pressão Sanguínea/fisiologia , HDL-Colesterol , Fatores de RiscoRESUMO
Accurate and reliable pose estimation of boom-type roadheaders is the key to the forming quality of the tunneling face in coal mines, which is of great importance to improve tunneling efficiency and ensure the safety of coal mine production. The multi-laser-beam target-based visual localization method is an effective way to realize accurate and reliable pose estimation of a roadheader body. However, the complex background interference in coal mines brings great challenges to the stable and accurate segmentation and extraction of laser beam features, which has become the main problem faced by the long-distance visual positioning method of underground equipment. In this paper, a semantic segmentation network for underground laser beams in coal mines, RCEAU-Net, is proposed based on U-Net. The network introduces residual connections in the convolution of the encoder and decoder parts, which effectively fuses the underlying feature information and improves the gradient circulation performance of the network. At the same time, by introducing cascade multi-scale convolution in the skipping connection section, which compensates for the lack of contextual semantic information in U-Net and improves the segmentation effect of the network model on tiny laser beams at long distance. Finally, the introduction of an efficient multi-scale attention module with cross-spatial learning in the encoder enhances the feature extraction capability of the network. Furthermore, the laser beam target dataset (LBTD) is constructed based on laser beam target images collected from several coal mines, and the proposed RCEAU-Net model is then tested and verified. The experimental results show that, compared with the original U-Net, RCEAU-Net can ensure the real-time performance of laser beam segmentation while increasing the Accuracy by 0.19%, Precision by 2.53%, Recall by 22.01%, and Intersection and Union Ratio by 8.48%, which can meet the requirements of multi-laser-beam feature segmentation and extraction under complex backgrounds in coal mines, so as to further ensure the accuracy and stability of long-distance visual positioning for boom-type roadheaders and ensure the safe production in the working face.
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This study presented a novel modification method for fine SiC powder by using sodium lignosulfonate as a dispersant. The adsorption behavior of sodium lignosulfonate on the SiC/water interface and its effect on the performance of a fine SiC slurry were systematically investigated. The adsorption results showed that sodium lignosulfonate formed monolayer adsorption on the surface of fine SiC and that the saturated adsorption capacity was 1.3263 mg/g. The adsorption reached equilibrium within 3 h and was mainly controlled by active sites on the SiC surface. The dispersion, stability, and zeta potential of modified SiC powder were improved after sodium lignosulfonate adsorption. The zeta potential of modified SiC reached a minimum value of -44.8 mV at pH 12. Modified SiC suspensions had great stability in a wider pH range of 6-12. Modified SiC slurry with 54 vol % solid loading had a low viscosity of 173 mPa·s at pH 10. Subsequently, coarse SiC powder was added for slip casting. A mixed slurry with high solid loading (69 vol %) and low viscosity (583 mPa·s) was prepared using modified SiC and coarse SiC powders at a mass ratio of 2:3. Finally, recrystallized SiC green body with high density (2.6492 g/cm3) was obtained.
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Intertemporal preference has been investigated mainly with a choice paradigm. However, a matching paradigm might be more informative for a proper inference about intertemporal preference and a deep understanding of the underlying cognitive mechanisms. This research involved two empirical studies using the matching paradigm and compared various corresponding dynamic models. These models were developed under either the framework of decision field theory, an exemplar theory assuming evidence accumulation, or a non-evidence-accumulation framework built upon the well-established notions of random utility and discrimination threshold (i.e., the RUDT framework). Most of these models were alternative-based whereas the others were attribute-based ones. Participants in Study 1 were required to fill in the amount of an immediate stimulus to make it as attractive as a delayed stimulus, whereas those in Study 2 needed to accomplish a more general matching task in which either the payoff amount or delay length of one stimulus was missing. Consistent behavioral regularities regarding both matching values and response times were revealed in these studies. The results of model comparison favored in general the RUDT framework as well as an attribute-based perspective on intertemporal preference. In addition, the predicted matching values and response times of the best RUDT model were also highly correlated with the observed data and replicated most observed behavioral regularities. Together, this research and previous modeling work on intertemporal choice suggest that evidence accumulation is not essential for generating intertemporal preference. Future research should examine the validity of the new framework in other preferential decisions for a more stringent test of the framework.
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Desvalorização pelo Atraso , Humanos , Desvalorização pelo Atraso/fisiologia , Comportamento de Escolha/fisiologia , Tempo de Reação , Cognição , RecompensaRESUMO
CuInS2 quantum dots (CIS QDs) are considered to be promising alternatives for Cd-based QDs in the fields of biology and medicine. However, high-quality hydrophobic CIS QDs are difficult to be transferred to water due to their 1-dodecylmercaptan (DDT) ligands. Therefore, the fluorescence and stability of the prepared aqueous CIS QDs is not enough to meet the requirement for sensitive detection. Here, as large as 13 nm CuInZnS/ZnS QDs with DDT ligands were first synthesized, and then, CuInZnS/ZnS microbeads (QBs) containing thousands of QDs were successfully fabricated by a two-step approach of emulsion-solvent evaporation and surfactant substitution. Through emulsion-solvent evaporation, the CuInZnS/ZnS QDs formed microbeads in the microemulsion with dodecyl trimethylammonium bromide (DTAB), and the Förster resonance energy transfer (FRET) has been effectively overcome. Then, CO-520 was introduced to substitute DTAB to improve the stability and water solubility. Lastly, the microbeads were coated with a SiO2 shell and carboxylated. Subsequently, the constructed QBs (â¼210 nm) were used as labels in a fluorescence immunosorbent assay (FLISA) for quantitative detection of heart type fatty acid binding protein (H-FABP), and the limit of detection was 0.48 ng mL-1, which indicated a greatly improved detection sensitivity compared to that of the Cd-free QDs. The highly fluorescent and stable CuInZnS/ZnS QBs will have great application prospects in many biological fields.
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Pontos Quânticos , Emulsões , Microesferas , Pontos Quânticos/química , Dióxido de Silício , Solventes , Sulfetos/química , Tensoativos , Água/química , Compostos de Zinco/químicaRESUMO
BACKGROUND: Limited evidence is available on the association between estimated cardiorespiratory fitness (e-CRF) and incidence of cardiovascular disease (CVD) in Chinese population. METHODS: A total of 10,507 adults including 5084 men (48.4%) and 5423 (51.6%) women with a median age of 56.0 (25% quantile: 49, 75% quantile 63) years from the China Health and Retirement Longitudinal Study (CHARLS) was recruited in 2011 as baseline. The CVD incident events were followed-up until 2018. e-CRF was calculated from sex-specific longitudinal non-exercise equations and further grouped into quartiles. Cox proportional models were used to calculate hazard ratio (HR) and 95% confidence interval (CI) for incidence risks of CVD, heart disease and stroke. RESULTS: During a median follow-up of 7 years, a total of 1862 CVD, 1409 heart disease and 612 stroke events occurred. In fully adjusted models, each one MET increment of e-CRF was associated with lower risk of CVD (HR = 0.91, 95%CI = 0.85-0.96 for males, HR = 0.87, 95%CI = 0.81-0.94 for females). Compared with the Quartile (Q)1 group, the HRs (95%CI) of the Q2, Q3 and Q4 groups were 0.84 (0.63-1.03), 0.72 (0.57-0.91) and 0.66 (0.51-0.87) for CVD in males. Females had HRs of 0.79 (0.66-0.96) in Q2, 0.71 (0.57-0.88) in Q3 and 0.58 (0.45-0.75) in Q4 for CVD. The associations between e-CRF and heart disease and stroke were slightly weaker than that for CVD in both males and females. CONCLUSIONS: Higher e-CRF decreases the incident risk of CVD, heart disease and stroke.
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Aptidão Cardiorrespiratória , Doenças Cardiovasculares , Cardiopatias , Acidente Vascular Cerebral , Adulto , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Doenças Cardiovasculares/epidemiologia , Estudos Longitudinais , Aptidão Física , Acidente Vascular Cerebral/epidemiologia , Fatores de RiscoRESUMO
Wearable optical fiber sensors have great potential for development in medical monitoring. With the increasing demand for compactness, comfort, accuracy, and other features in new medical monitoring devices, the development of wearable optical fiber sensors is increasingly meeting these requirements. This paper reviews the latest evolution of wearable optical fiber sensors in the medical field. Three types of wearable optical fiber sensors are analyzed: wearable optical fiber sensors based on Fiber Bragg grating, wearable optical fiber sensors based on light intensity changes, and wearable optical fiber sensors based on Fabry-Perot interferometry. The innovation of wearable optical fiber sensors in respiration and joint monitoring is introduced in detail, and the main principles of three kinds of wearable optical fiber sensors are summarized. In addition, we discuss their advantages, limitations, directions to improve accuracy and the challenges they face. We also look forward to future development prospects, such as the combination of wireless networks which will change how medical services are provided. Wearable optical fiber sensors offer a viable technology for prospective continuous medical surveillance and will change future medical benefits.
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Fibras Ópticas , Dispositivos Eletrônicos Vestíveis , Estudos Prospectivos , Luz , InterferometriaRESUMO
The suboccipital cavernous sinus (SCS) and the myodural bridge complex (MDBC) are both located in the suboccipital region. The SCS is regarded as a route for venous intracranial outflow and is often encountered during surgery. The MDBC consists of the suboccipital muscles, nuchal ligament, and myodural bridge and could be a power source for cerebrospinal fluid circulation. Intracranial pressure depends on intracranial blood volume and the cerebrospinal fluid. Since the SCS and MDBC have similar anatomical locations and functions, the aim of the present study was to reveal the relationships between them and the detailed anatomical characteristics of the SCS. The study involved gross dissection, histological staining, P45 plastination, and three-dimensional visualization techniques. The SCS consists of many small venous sinuses enclosed within a thin fibrous membrane that is strengthened by a fibrous arch closing the vertebral artery groove. The venous vessels are more abundant in the lateral and medial portions of the SCS than the middle portion. The middle and medial portions of the SCS are covered by the MDBC. Type I collagen fibers arranged in parallel and originating from the MDBC terminate on the SCS either directly or indirectly via the fibrous arch. The morphological features of SCS revealed in this research could serve as an anatomical basis for upper neck surgical procedures. There are parallel arrangements of type I collagen fibers between the MDBC and the SCS. The MDBC could change the blood volume in the SCS by pulling its wall during the head movement.
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Seio Cavernoso , Vértebras Cervicais , Humanos , Vértebras Cervicais/anatomia & histologia , Colágeno Tipo I , Dura-Máter/anatomia & histologia , Pescoço/anatomia & histologiaRESUMO
BACKGROUND: Research on glucosamine shows anti-inflammatory and anti-cancer benefits with minimal adverse effects. We aimed to explore the relationship between use of glucosamine and risk of lung cancer and lung cancer mortality based on data from the large-scale nationwide prospective UK Biobank cohort study. METHODS: Participants were enrolled between 2006 and 2010 and followed-up to 2020. The Cox proportional hazards model was used to assess the relationship between glucosamine use and risk of lung cancer and lung cancer mortality. Subgroup analyses and sensitivity analyses were performed to explore the potential effect modifications and the robustness of the main findings. RESULTS: 439â393 participants (mean age 56â years; 53% females) with a mean follow-up of 11â years were included for analyses. 82â603 (18.80%) participants reported regular use of glucosamine at baseline. During follow-up, 1971 (0.45%) lung cancer events were documented. Glucosamine use was significantly associated with a decreased risk of lung cancer (hazard ratio (HR) 0.84, 95% CI 0.75-0.92; p<0.001) and lung cancer mortality (HR 0.88, 95% CI 0.81-0.96; p=0.002) in fully adjusted models. A stronger association between glucosamine use and decreased lung cancer risk was observed in participants with a family history of lung cancer when compared with those without a family history. CONCLUSION: Regular use of glucosamine was significantly related with decreased risk of lung cancer and lung cancer mortality, based on data from this nationwide prospective cohort study.
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Glucosamina , Neoplasias Pulmonares , Estudos de Coortes , Feminino , Glucosamina/efeitos adversos , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de RiscoRESUMO
The 5' untranslated regions (5' UTR) of mRNAs play an important role in the eukaryotic translation initiation process. Additional levels of translational regulation may be mediated through interactions between structured mRNAs that can adopt interchangeable secondary or tertiary structures and the regulatory protein/RNA factors or components of the translational apparatus. Here we report a regulatory function of the 5' UTR mRNA of the spe2 gene (SAM decarboxylase) in polyamine metabolism of the fission yeast Schizosaccharomyces pombe Reporter assays, biochemical experiments, and mutational analysis demonstrate that this 5' UTR mRNA of spe2 can bind to spermidine to regulate translation. A tertiary structure transition in the 5' UTR RNA upon spermidine binding is essential for translation regulation. This study provides biochemical evidence for spermidine binding to regulate translation of the spe2 gene through interactions with the 5' UTR mRNA. The identification of such a regulatory RNA that is directly associated with an essential eukaryotic metabolic process suggests that other ligand-binding RNAs may also contribute to eukaryotic gene regulation.
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Regiões 5' não Traduzidas , Adenosilmetionina Descarboxilase/genética , Biossíntese de Proteínas/efeitos dos fármacos , RNA Mensageiro/metabolismo , Schizosaccharomyces/genética , Espermidina/metabolismo , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Genes Reporter , Ligantes , RNA Fúngico/genética , RNA Fúngico/metabolismo , RNA Mensageiro/genética , Schizosaccharomyces/metabolismoRESUMO
The 5' untranslated region (5' UTR) of eukaryotic mRNA plays an important role in translation. Here we report the function of the 5' UTR mRNA of S-adenosylmethionine synthetase (sam1) in translational modulation in the presence of SAM in fission yeast Schizosaccharomyces pombe Reporter assays, binding and chemical probing experiments, and mutational analysis show that the 5' UTR mRNA of sam1 binds to SAM to effect translation. Translational modulation is dependent on a tertiary structure transition in the RNA upon SAM binding. The characterization of such an RNA that is directly associated with an essential metabolic process in eukaryotes provides additional evidence that ligand binding by RNAs plays an important role in eukaryotic gene regulation.
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Regiões 5' não Traduzidas , Metionina Adenosiltransferase/genética , Biossíntese de Proteínas/efeitos dos fármacos , RNA Mensageiro/metabolismo , S-Adenosilmetionina/metabolismo , Schizosaccharomyces/genética , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Genes Reporter , Ligantes , RNA Fúngico/genética , RNA Fúngico/metabolismo , RNA Mensageiro/genética , Schizosaccharomyces/metabolismoRESUMO
Microbe-mediated transformations of arsenic (As) often require As to be taken up into cells prior to enzymatic reaction. Despite the importance of these microbial reactions for As speciation and toxicity, understanding of how As bioavailability and uptake are regulated by aspects of extracellular water chemistry, notably dissolved organic matter (DOM), remains limited. Whole-cell biosensors utilizing fluorescent proteins are increasingly used for high-throughput quantification of the bioavailable fraction of As in water. Here, we present a mathematical framework for interpreting the time series of biosensor fluorescence as a measure of As uptake kinetics, which we used to evaluate the effects of different forms of DOM on uptake of trivalent arsenite. We found that thiol-containing organic compounds significantly inhibited uptake of arsenite into cells, possibly through the formation of aqueous complexes between arsenite and thiol ligands. While there was no evidence for competitive interactions between arsenite and low-molecular-weight neutral molecules (urea, glycine, and glyceraldehyde) for uptake through the aquaglyceroporin channel GlpF, which mediates transport of arsenite across cell membranes, there was evidence that labile DOM fractions may inhibit arsenite uptake through a catabolite repression-like mechanism. The observation of significant inhibition of arsenite uptake at DOM/As ratios commonly encountered in wetland pore waters suggests that DOM may be an important control on the microbial uptake of arsenite in the environment, with aspects of DOM quality playing an important role in the extent of inhibition. IMPORTANCE The speciation and toxicity of arsenic in environments like rice paddy soils and groundwater aquifers are controlled by microbe-mediated reactions. These reactions often require As to be taken up into cells prior to enzymatic reaction, but there is limited understanding of how microbial arsenic uptake is affected by variations in water chemistry. In this study, we explored the effect of dissolved organic matter (DOM) quantity and quality on microbial As uptake, with a focus on the role of thiol functional groups that are well known to form aqueous complexes with arsenic. We developed a quantitative framework for interpreting fluorescence time series from whole-cell biosensors and used this technique to evaluate effects of DOM on the rates of microbial arsenic uptake. We show that thiol-containing compounds significantly decrease rates of As uptake into microbial cells at environmentally relevant DOM/As ratios, revealing the importance of DOM quality in regulating arsenic uptake, and subsequent biotransformation, in the environment.
Assuntos
Arsênio , Arsenitos , Técnicas Biossensoriais , Poluentes Químicos da Água , Arsênio/análise , Bactérias , Matéria Orgânica Dissolvida , Compostos de Sulfidrila , Água , Poluentes Químicos da Água/análiseRESUMO
As a carbon-free energy carrier and an attractive alternative energy source, hydrogen energy has great development potential for future considerations, and it may be the ultimate answer to the global energy crisis. Due to the high combustibility of hydrogen, hydrogen sensors will be a vital component of safe use of hydrogen. Among the various sensors, the optical hydrogen sensor can meet the requirements of intrinsic safety, online detection, surrounding immunity, and lack of spark. Hence, we demonstrate a miniature optics-mechanics synergistic fiber optic hydrogen sensor by using Pd nanofilm, it has a large response range (0.5%-3.5%), high sensitivity of -0.334â nm/1% concentration and a short response time (10s)/recovery time (25s). Experimental results reveal that the proposed optics-mechanics synergistic fiber optic hydrogen sensor is reusable, durable, and low temperature sensitive. In this optics-mechanics synergistic fiber optic hydrogen sensor, nano Pd film with a large surface-to-volume ratio allows for rapid hydrogen dissociation, and Pd lattice expansion caused by Pd-hydrogen reaction is effectively transduced into optical change. This proposed sensor integrated Pd nanofilm with optical fiber by using an optics-mechanics synergistic strategy, resulting in a compact and all-optical solution for the safe measurement of hydrogen concentration, which can be used in hazardous or space-limited environments.